rs3756505

chr5-149506960-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001892.6(CSNK1A1):c.857+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,177,532 control chromosomes in the GnomAD database, including 8,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1659 hom., cov: 32)
  • Exomes 𝑓: 0.11 (6417 hom.)
• Consequence: CSNK1A1 NM_001892.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

Genes affected

CSNK1A1 (HGNC:2451): (casein kinase 1 alpha 1) Enables protein serine/threonine kinase activity. Involved in several processes, including negative regulation of canonical Wnt signaling pathway; peptidyl-serine phosphorylation; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in centrosome; cytosol; and nuclear speck. Part of beta-catenin destruction complex. Colocalizes with keratin filament and mRNA cleavage and polyadenylation specificity factor complex. Biomarker of Alzheimer's disease and inclusion body myositis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK1A1	NM_001892.6	c.857+67A>G		intron_variant		ENST00000377843.8
CSNK1A1	NM_001025105.3	c.941+67A>G		intron_variant
CSNK1A1	NM_001271741.2	c.857+67A>G		intron_variant
CSNK1A1	NM_001271742.2	c.674+67A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1A1	ENST00000377843.8	c.857+67A>G		intron_variant		1	NM_001892.6	A1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20878 AN: 152114 Hom.: 1661 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.106 AC: 109141 AN: 1025300 Hom.: 6417 AF XY: 0.105 AC XY: 54167 AN XY: 517866

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.0606

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0995

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.137 AC: 20916 AN: 152232 Hom.: 1659 Cov.: 32 AF XY: 0.136 AC XY: 10095 AN XY: 74438

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.137

Alfa AF: 0.117 Hom.: 1120

Bravo AF: 0.146

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.8
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3756505; hg19: chr5-148886523; COSMIC: COSV55796453; COSMIC: COSV55796453;